This project will investigate the mechanisms of glomerular injury in an experimental model associated with granular immune deposits along the subepithelial aspect of the glomerular capillary wall. Previous studies have shown that these deposits are dependent on properties of the glomerulus itself, and that they form locally rather than from circulating immune complex trapping previously believed. Further studies will utilize radiolabelled antibody to define the kinetics of immune deposit formation in experimental membranous nephropathy and the relationship between proteinuria and quantity of antibody deposited. The role of complement and neutrophils in mediating proteinuria will be studied and the effect of alterations in antibody size, charge and structure on subepithelial deposit formation will be evaluated. The isolated perfused rat kidney system will be utilized to study in vitro the mechanism of deposit formation using antibody eluted from deposits formed in vivo and to study mechanisms of proteinuria in experimental glomerulonephritis. The overall objective of this project will be to further define the mechanisms of subepithelial immune deposit formation and the way in which this apparently new immunopathogenetic mechanism mediated glomerular injury.